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NCT Number: NCT07721688

Different Frequency Temporal Interference Stimulation on Bilateral Subthalamic Nucleus for Parkinson's Disease

This clinical trial will evaluate the efficacy of accelerated Temporal Interference Stimulation (TIS) as a therapeutic intervention for individuals diagnosed with Parkinson's disease. Different frequency TIS will be delivered targeting the bilateral subthalamic nuclei of the brain according to the patient's clinical symptoms. Specifically, the basal thalamic nuclei on the side opposite to the side where the patient's symptoms are most severe receive stimulation at 130 Hz, whilst those on the other side receive stimulation at 60 Hz. The primary objective is to assess whether accelerated TIS yields measurable improvements in motor performance and verbal speech function among enrolled subjects. Functional magnetic resonance imaging (fMRI) will be adopted as an auxiliary imaging modality to objectively characterize underlying cerebral functional alterations induced by accelerated TIS intervention. The core scientific research questions to be addressed in this trial are listed as follows:

Will accelerated TIS administered to the bilateral subthalamic nuclei produce significant improvements in motor function and cognitive function among enrolled subjects with Parkinson-related disorders? What quantitative and qualitative modifications in cerebral functional activity will be detected via fMRI after standardized accelerated TIS intervention administration? Investigators will implement a two-arm parallel controlled comparative design for all enrolled eligible subjects. All confirmed Parkinson's disease patients will undergo standardized random grouping and be allocated into two independent research arms. Subjects in the experimental arm will receive continuous, standardized TIS intervention targeting bilateral subthalamic nuclei. Subjects in the control arm will receive matched sham stimulation intervention. Sham stimulation adopts identical operation procedures, equipment wearing mode and on-site operating environment as formal TIS, with no valid neuromodulation therapeutic effect generated. Rigorous controlled grouping design will ensure objective, verifiable data support for verifying the actual intervention efficacy of different frequency TIS on motor dysfunction and speech impairment in Parkinson-related patients.

All enrolled subjects will complete the following standardized trial procedures in full compliance with the trial protocol:

Receive continuous targeted intervention of either formal TIS or matched sham stimulation on bilateral subthalamic nuclei, with consecutive 5-day fixed-course administration in strict accordance with trial operating specifications.

Complete unified fMRI brain scanning examinations and standardized motor function as well as speech function quantitative evaluation assessments at two fixed time nodes, including the baseline time point before intervention initiation and the follow-up time point after all intervention courses are completed.

Truthfully record all adverse reactions and abnormal physical discomfort symptoms that occur throughout the whole intervention and follow-up observation cycle in standardized adverse event registration forms.

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Key information

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510000, China

Location status: Recruiting

Location contact

Liu Hanjun

CONTACT

[email protected]

+86 15920175118

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Idiopathic Parkinson's disease diagnosed by neurologists according to the Movement Disorder Society Clinical Diagnostic Criteria;
  • Hoehn and Yahr stage 1.5-3.0;
  • Stable levodopa-based antiparkinsonian medication for at least 4 weeks before enrolment, with no planned medication change during the trial period;
  • Ability to walk independently;
  • Ability to understand and follow study instructions and complete the required assessments, with no severe cognitive impairment as screened by the Montreal Cognitive Assessment and/or Mini-Mental State Examination according to prespecified thresholds;
  • Willingness to participate and provide written informed consent.

Exclusion criteria

  • Any contraindication to MRI or tTIS, including claustrophobia or ferromagnetic intracranial or subcutaneous implants;
  • Significant systemic disease that could increase study risk or interfere with trial participation;
  • Neurological disorders other than Parkinson's disease;
  • Major psychiatric disorder or severe depression or anxiety;
  • History of deep brain stimulation surgery;
  • Inability or unwillingness to complete all interventions and assessments.

Treatment and study plan

temporal interference stimulation

Device

Sequential bilateral subthalamic nucleus (STN) temporal interference electrical stimulation, administered twice daily (40 minutes per session, ≥1 hour rest interval between sessions). Stimulation targets are bilateral STN, with individualized electrode placement and current intensity determined via personalized modeling from patient MRI data. A fixed carrier frequency of 2000 Hz is used for all STN stimulation. Specifically, therapeutic temporal interference stimulation with an envelope frequency of 130 Hz is delivered to the STN contralateral to the patient's most symptomatic side, while stimulation with an envelope frequency of 60 Hz is applied to the STN ipsilateral to the most symptomatic side to produce targeted therapeutic interference fields.

Other names: TIS, TI Stimulation, TI, tTIS, Transcranial Temporal Interference Stimulation

Primary outcomes

  1. The score of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III)

    Time frame: From enrollment to 1 month after treatment

    The MDS-UPDRS-III is a standardized assessment tool to evaluate motor function symptoms in people with Parkinson's disease.It has a scoring range of 0 to 132 points, with higher scores meaning more severe motor disorders.

Secondary outcomes

  1. The scores of Mini-BESTest

    Time frame: From enrollment to 1 month after treatment

    The Mini-BESTest is a clinical assessment tool for evaluating balance function. It assesses the balance control system across multiple domains, with a scoring range of 0 to 28 points; higher scores indicate better balance function.

  2. 10-Meter Walk Test

    Time frame: From the enrollment to 1 month after treatment

    The 10-Meter Walk Test assesses gait speed and functional mobility by measuring the time required to walk 10 meters. Increased time reflects slower walking and worse mobility.

  3. Voice intensity

    Time frame: From the enrollment to 1 month after treatment

    Voice intensity is measured using Praat software. Voice intensity, expressed in dB SPL, reflects the loudness of the voice. This indicators is used to objectively evaluate the functional status of the subjects' vocal system. Abnormalities in voice intensity may indicate impairments in vocal cord movement, laryngeal muscle control, or related neural regulation, which is of great significance for assessing the severity of vocal function disorders and the effect of intervention.

  4. Velocity of center of pressure (COP) sway

    Time frame: From the enrollment to 1 month after treatment

    Center of pressure (COP) sway velocity of subjects on stable and unstable surfaces is measured via a balance board during two standing conditions: single-task quiet standing and dual-task standing. The dual-task standing requires subjects to continuously perform serial subtraction of 7 from random numbers ranging from 400 to 600 while maintaining standing posture. The balance board records COP movement speed under both single-task and dual-task standing states. This indicator objectively assesses balance control and adaptability to different surfaces; abnormal increases indicate impaired balance, aiding evaluation of balance disorder severity and intervention effectiveness.

  5. BOLD-fMRI

    Time frame: From the enrollment to 1 month after treatment

    Functional MRI is used to acquire BOLD data. BOLD signals reflect regional brain activity and functional connectivity. This measure evaluates brain function and structural connectivity associated with motor and cognitive performance.

  6. Phonation duration

    Time frame: From the enrollment to 1 month after treatment

    Phonation duration refers to the continuous time of voluntary phonation. This indicators is used to objectively evaluate the functional status of the subjects' vocal system. Abnormalities in phonation duration may indicate impairments in vocal cord movement, laryngeal muscle control, or related neural regulation, which is of great significance for assessing the severity of vocal function disorders and the effect of intervention.

  7. Fundamental frequency (F₀)

    Time frame: From the enrollment to 1 month after treatment

    Fundamental frequency (F₀) range of subjects' phonation is measured using Praat software. Fundamental frequency range is the interval between the minimum and maximum F₀ (unit: Hz) during phonation, reflecting the variability of voice pitch. This indicators is used to objectively evaluate the functional status of the subjects' vocal system. Abnormalities in F₀ range may indicate impairments in vocal cord movement, laryngeal muscle control, or related neural regulation, which is of great significance for assessing the severity of vocal function disorders and the effect of intervention.

  8. Range of center of pressure (COP) sway

    Time frame: From the enrollment to 1 month after treatment

    Center of pressure (COP) sway range of subjects on stable and unstable surfaces is measured via a balance board during two standing conditions: single-task quiet standing and dual-task standing. The dual-task standing requires subjects to continuously perform serial subtraction of 7 from random numbers ranging from 400 to 600 while maintaining standing posture. The balance board records the maximum displacement range of COP deviation under both single-task and dual-task standing states. This indicator objectively assesses postural stability and balance regulation ability on different surfaces; abnormal increases indicate deteriorated postural control, aiding evaluation of balance disorder severity and intervention effectiveness.

  9. Path of center of pressure (COP) sway

    Time frame: From the enrollment to 1 month after treatment

    Center of pressure (COP) sway path of subjects on stable and unstable surfaces is measured via a balance board during two standing conditions: single-task quiet standing and dual-task standing. The dual-task standing requires subjects to continuously perform serial subtraction of 7 from random numbers ranging from 400 to 600 while maintaining standing posture. The balance board records the total traveling path length of COP movement under both single-task and dual-task standing states. This indicator objectively reflects the complexity and stability of postural adjustment during standing on different surfaces; abnormal increases indicate inefficient balance control and postural instability, aiding evaluation of balance disorder severity and intervention effectiveness.

  10. Area of center of pressure (COP) sway

    Time frame: From the enrollment to 1 month after treatment

    Center of pressure (COP) sway area of subjects on stable and unstable surfaces is measured via a balance board during two standing conditions: single-task quiet standing and dual-task standing. The dual-task standing requires subjects to continuously perform serial subtraction of 7 from random numbers ranging from 400 to 600 while maintaining standing posture. The balance board records the planar enclosed area covered by continuous COP movement under both single-task and dual-task standing states. This indicator objectively evaluates the overall stability of standing posture and anti-interference ability on different surfaces; abnormal increases represent expanded postural sway range and impaired balance function, aiding evaluation of balance disorder severity and intervention effectiveness.

  11. Diffusion Tensor Imaging(DTI)

    Time frame: From the enrollment to 1 month after treatment

    Functional MRI is used to acquire Diffusion Tensor Imaging(DTI) data. DTI characterizes white matter microstructural integrity and fiber tract organization. This measure evaluates brain function and structural connectivity associated with motor and cognitive performance.

  12. Timed Up and Go (TUG) Test Time

    Time frame: From the enrollment to 1 month after treatment

    The time consumed by subjects to complete the standard Timed Up and Go (TUG) test is recorded as the evaluation outcome. During the test, subjects are required to finish a series of standardized movements including standing up from a chair, straight walking, turning around, and sitting back down independently. This indicator objectively assesses basic walking ability, functional mobility and gross motor control ability of subjects; prolonged completion time indicates impaired walking and mobility function, aiding the evaluation of motor dysfunction severity and intervention effectiveness.

  13. Dual-Task Timed Up and Go (Dual-Task TUG) Test Time

    Time frame: From the enrollment to 1 month after treatment

    The time consumed by subjects to complete the dual-task Timed Up and Go (TUG) test is recorded as the evaluation outcome. During the dual-task test, subjects are required to finish the entire standard TUG motor sequence while simultaneously performing continuous serial subtraction of 7 from random numbers within 100, which imposes additional cognitive load during walking. This indicator comprehensively reflects subjects' dual-task execution ability, integrating walking mobility and cognitive-motor coordination capacity. Increased completion time represents declined dual-task processing efficiency and compromised gait stability under cognitive interference, aiding the evaluation of comprehensive motor-cognitive function and intervention effectiveness.

Study contacts

Contact information is provided by the study sponsor or research team.

Sponsors and collaborators

Lead sponsor

Ke Dong, MD

Other

Registry information

Official study title

A Single-Center, Double-Blind Randomized Controlled Trial of Different Frequency Temporal Interference Stimulation Applied to Bilateral Subthalamic Nucleus for Improving Motor and Vocal Functions in Patients With Parkinson's Disease.

Important dates

Study start
2026
Primary completion
2026
Study completion
2026
First posted
Jul 23, 2026
Registry last updated
Jul 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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